Endothelial dysfunction caused by circulating microparticles from diabetic mice is reduced by PD98059 through ERK and ICAM-1.

Kumiko Taguchi, Nozomu Kaneko, Kanami Okudaira, Takayuki Matsumoto, Tsuneo Kobayashi

European journal of pharmacology 2021 Dec 15

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Endothelial dysfunction contributes to the development of diabetic complications and the production of circulating microparticles (MPs). Our previous study showed that diabetic mice-derived MPs (DM MPs) had increased levels of extracellular regulated protein kinase 1/2 (ERK1/2) and impaired endothelial-dependent relaxation in aortas when compared with control mice-derived MPs. This study was designed to investigate whether PD98059, an ERK1/2 inhibitor, affects the function of aortas and DM MPs. MPs were obtained from streptozotocin-induced DM, DM after PD98059 treatment, and ICR mice as control. The mice and MPs were then analyzed on the basis of their vascular function and enzyme expressions. Compared with the controls, platelet-derived MPs and ERK1/2 levels in the MPs were significantly elevated in the DM but showed little change in PD98059-treated DM. PD98059 mainly decreased ERK1/2 phosphorylation in the MPs. In the aortas of DM and DM MPs the endothelium-dependent vascular function was impaired, and there was a significantly greater improvement in the vascular function in the PD98059-treated DM aortas and the aortas treated with PD98059-treated DM MPs than in DM aortas and the aortas treated with DM MPs. Furthermore, DM MPs increased ERK1/2 and intracellular adhesion molecule-1 (ICAM-1) expressions in the aortas, but PD98059-treated DM MPs did not show these effects. For the first time, these results indicate that PD98059 treatment improves endothelial dysfunction in DM, and adhesion properties of DM MPs can be partly blocked by PD98059 via ERK and ICAM-1. These effects may explain some of the vascular complications in diabetes. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Kumiko Taguchi, Nozomu Kaneko, Kanami Okudaira, Takayuki Matsumoto, Tsuneo Kobayashi. Endothelial dysfunction caused by circulating microparticles from diabetic mice is reduced by PD98059 through ERK and ICAM-1. European journal of pharmacology. 2021 Dec 15;913:174630